The Journal of Organic Chemistry
Article
(neat): 2922, 2854, 2356, 2334, 1668, 1567, 1467, 1290, 1159, 1104,
1020, 752 cm−1. 1H NMR (400 MHz, CDCl3): δ, 7.58 (d, J = 0.9 Hz,
2H), 7.22 (d, J = 3.5 Hz, 2H), 7.20−7.14 (m, 2H), 7.14−7.07 (m,
2H), 5.44 (dd, J = 9.2, 3.1 Hz, 1H), 4.20−4.00 (m, 1H), 3.84−3.62
(m, 1H), 3.43 (dd, J = 15.4, 9.3 Hz, 1H), 3.17 (dd, J = 15.4, 3.5 Hz,
1H), 3.07−2.90 (m, 1H), 2.70 (dt, J = 16.3, 3.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ, 187.0, 153.0, 146.6, 137.3, 134.0, 129.1, 126.6,
126.3, 124.6, 117.7, 112.3, 72.6, 63.2, 45.3, 28.8. HRMS (ESI, m/z):
calculated for C15H14NaO3 ([M + Na]+), 265.0835; found, 265.0837;
117.8, 112.9 (d, J = 21.5 Hz), 112.4, 72.2 (d, J = 2.2 Hz), 62.5, 45.0,
22.0 (d, J = 3.5 Hz). HRMS (ESI, m/z): calculated for C15H13FNaO3
22
([M + Na]+), 283.0741; found, 283.0765; [α]D = +92.60 (c = 0.5,
CHCl3, 90% ee). The enantiomeric ratio was determined by HPLC
analysis using a Daicel Chiralpak IC-3 column (hexane/2-propanol =
80:20, flow rate 1.0 mL/min, λ = 254 nm), tR = 23.1 min (major), tR =
15.6 min (minor).
1-(Furan-2-yl)-2-(7-methylisochroman-1-yl)ethanone (2l). 24 mg;
82% yield; Rf = 0.36 (10:90 = EtOAc/n-hexane); colorless liquid. FT-
IR (neat): 2922, 2854, 2370, 1673, 1566, 1467, 1395, 1292, 1160,
1106, 1025, 808, 766, 645, 595 cm−1. 1H NMR (400 MHz, CDCl3): δ,
7.59 (d, J = 0.9 Hz, 1H), 7.23 (d, J = 3.4 Hz, 1H), 7.09 (m, 2H), 6.91
(s, 1H), 6.53 (dd, J = 3.5, 1.7 Hz, 1H), 5.40 (dd, J = 9.3, 2.6 Hz, 1H),
4.08 (m, 1H), 3.75 (m, 1H), 3.42 (dd, J = 15.4, 9.5 Hz, 1H), 3.17 (dd,
J = 15.4, 3.4 Hz, 1H), 3.02 (m, 1H), 2.66 (dt, J = 16.1, 3.8 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ, 187.0, 153.1, 146.6, 137.1, 135.8,
130.9, 128.9, 127.5, 125.1, 117.7, 112.3, 72.6, 63.3, 45.4, 28.5, 21.2.
HRMS (ESI, m/z): calculated for C16H16NaO3 ([M + Na]+),
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[α]D = +93.26 (c = 0.85, CHCl3, 96% ee). The enantiomeric ratio
was determined by HPLC analysis using a Daicel Chiralpak IC-3
column (hexane/2-propanol = 80:20, flow rate 1.0 mL/min, λ = 254
nm), tR = 34.9 min (major), tR = 22.2 min (minor).
1-(4-Bromophenyl)-2-(isochroman-1-yl)ethanone (2h). 52 mg,
71% yield; Rf = 0.24 (10:80 = EtOAc/n-hexane); colorless solid;
mp. 126−128 °C. FT-IR (neat): 3042, 2920, 2362, 1731, 1586, 1463,
1377, 741 cm−1. 1H NMR (400 MHz, CDCl3): δ, 7.85 (d, J = 8.6 Hz,
2H), 7.59 (d, J = 8.6 Hz, 2H), 7.22−7.16 (m, 2H), 7.16−7.11 (m,
1H), 7.10−7.05 (m, 1H), 5.44 (dd, J = 8.7, 2.8 Hz, 1H), 4.08 (ddd, J =
11.3, 5.3, 3.5 Hz, 1H), 3.78 (ddd, J = 11.3, 9.9, 3.7 Hz, 1H), 3.55 (dd, J
= 16.0, 8.9 Hz, 1H), 3.25 (dd, J = 16.0, 3.4 Hz, 1H), 3.11−2.83 (m,
1H), 2.69 (dt, J = 16.2, 3.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ,
197.3, 136, 134, 131.9 (2C),129.9 (2C), 129.1, 128.3, 126.7, 126.3,
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279.0992; found, 279.1016; [α]D = +105.96 (c = 0.68, CHCl3,
94% ee). The enantiomeric ratio was determined by HPLC analysis
using a Daicel Chiralpak IC-3 column (hexane/2-propanol = 80:20,
flow rate 1.0 mL/min, λ = 254 nm), tR = 40.0 min (major), tR = 21.7
min (minor).
124.5, 123.0, 72.8, 63.6, 45.4, 28.9. HRMS (ESI, m/z): [M − H]+
2-(7-Fluoroisochroman-1-yl)-1-(furan-2-yl)ethanone (2m). 23
mg; 72% yield; Rf = 0.29 (20:80 = EtOAc/n-hexane); light yellow
colored semi solid. FT-IR (neat): 2854, 2922, 2359, 1669, 1567, 1498,
28
calculated for C17H14BrO2, 329.0140; found 329.0172; [α]D
=
+3.357 (c = 0.333, CHCl3, 96% ee). The enantiomeric ratio was
determined by HPLC analysis using a Daicel Chiralpak IC-3 column
(hexane/2-propanol = 90:10, flow rate 1.0 mL/min, λ = 254 nm), tR =
8.9 min (major), tR = 6.9 min (minor).
1
1467, 1234, 1104, 1018, 764 cm−1. H NMR (400 MHz, CDCl3): δ,
7.58 (d, J = 1.0 Hz, 1H), 7.23 (d, J = 3.5 Hz, 1H), 7.05 (dd, J = 8.5, 5.6
Hz, 1H), 6.91−6.79 (m, 2H), 6.53 (dd, J = 3.5, 1.7 Hz, 1H), 5.38 (dd,
J = 8.3, 2.4 Hz, 1H), 4.14−4.01 (m, 1H), 3.76 (m, 1H), 3.40 (dd, J =
15.5, 9.1 Hz, 1H), 3.15 (dd, J = 15.5, 3.7 Hz, 1H), 3.04−2.90 (m, 1H),
2.68 (dt, J = 16.4, 3.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ,
186.8, 161.3 (d, J = 245.5 Hz), 153.0, 146.6, 136.2 (d, J = 7.6 Hz),
132.9 (d, J = 3.1 Hz), 126.2 (d, J = 8.2 Hz), 117.8, 115.3 (d, J = 20.7
Hz), 113.4 (d, J = 21.6 Hz), 112.4, 72.4, 62.9, 45.3, 28.9 (d, J = 1.3
Hz). HRMS (ESI, m/z): calculated for C15H13FNaO3 ([M + Na]+),
2-(Isochroman-1-yl)-1-(thiophen-2-yl)ethanone (2i). 37 mg, 64%
yield; Rf = 0.31 (10:90 = EtOAc/n-hexane); colorless oil. FT-IR
(neat): 2924, 2852, 1654, 1414, 1283, 1105, 1013, 855, 748, 699 cm−1;
1H NMR (400 MHz, CDCl3): δ, 7.74 (dd, J = 3.81 Hz, 0.89 Hz, 1H),
7.65 (dd, J = 4.97, 0.97 Hz, 1H), 7.18 (m, 2H), 7.12 (m, 3H), 5.46 (m,
1H), 4.11 (m, 1H), 3.79 (m, 1H), 3.50 (dd, J = 15.86, 8.96 Hz, 1H),
3.25 (dd, J = 15.63, 3.50 Hz, 1H), 2.99 (m, 1H), 2.70 (dt, J = 16.26,
3.51 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ, 190.9, 144.8, 137.4,
134.1, 132.5, 132.4, 129.1, 128.1, 126.7, 126.3, 124.6, 72.9, 63.5, 46.3,
28.9. HRMS (ESI, m/z): [M + H]+ calculated for C15H15O2S,
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283.0741; found, 283.0763; [α]D = +70.93 (c = 0.63, CHCl3, 95%
ee). The enantiomeric ratio was determined by HPLC analysis using a
Daicel Chiralpak IC-3 column (hexane/2-propanol = 80:20, flow rate
1.0 mL/min, λ = 254 nm), tR = 24.9 min (major), tR = 16.9 min
(minor).
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259.0787; found, 259.0792; [α]D = +17.20 (c = 0.22, CHCl3, 94%
ee). The enantiomeric ratio was determined by HPLC analysis using a
Daicel Chiralpak IC-3 column (hexane/2-propanol = 90:10, flow rate
1.0 mL/min, λ = 254 nm), tR = 20.58 min (minor), tR = 26.84 min
(major).
2-(6,7-Dimethoxyisochroman-1-yl)-1-(furan-2-yl)ethanone (2n).
27 mg; 75% yield; Rf = 0.2 (30:70 = EtOAc/n-hexane); colorless
crystalline solid; mp. 136−138 °C. FT-IR (neat): 2919, 2852, 2356,
2337, 1648, 1517, 1467, 1225, 1090, 1022, 994, 917, 852, 786, 733
2-(7,8-Dihydro-5H-[1,3]dioxolo[4,5-g]isochromen-5-yl)-1-(furan-
2-yl)ethanone (2j). 36 mg; 72% yield; Rf = 0.26 (30:70 = EtOAc/n-
hexane); colorless liquid. FT-IR (neat): 2923, 2853, 1668, 1485, 1467,
1
cm−1. H NMR (400 MHz, CDCl3): δ, 7.59 (s, 1H), 7.23 (d, J = 3.4
Hz, 1H), 6.58 (d, J = 11.3 Hz, 2H), 6.54−6.52 (m, 1H), 5.36 (dd, J =
8.7, 2.9 Hz, 1H), 4.07 (m, 1H), 3.82 (d, J = 18.8 Hz, 6H), 3.75 (m,
1H), 3.42 (dd, J = 15.2, 9.0 Hz, 1H), 3.11 (dd, J = 15.3, 3.6 Hz, 1H),
2.88 (m, 1H), 2.61 (d, J = 16.1 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ, 187.1, 153.1, 147.8, 147.5, 146.6, 129.0, 126.0, 117.8,
112.3, 111.6, 107.7, 72.4, 63.1, 56.0, 55.9, 45.5, 28.3. HRMS (ESI, m/
z): calculated for C17H18NaO5 ([M + Na]+), 325.1046; found,
1
1386, 1233, 1106, 1036, 766 cm−1. H NMR (400 MHz, CDCl3): δ,
7.58 (s, 1H), 7.22 (d, J = 3.5 Hz, 1H), 6.56 (s, 2H), 6.52 (dd, J = 3.5,
1.6 Hz, 1H), 5.88 (s, 2H), 5.32 (dd, J = 9.0, 2.8 Hz, 1H), 4.03 (m,
1H), 3.71 (m, 1H), 3.37 (dd, J = 15.4, 9.2 Hz, 1H), 3.09 (dd, J = 15.4,
3.5 Hz, 1H), 2.92−2.79 (m, 1H), 2.59 (dt, J = 16.0, 3.8 Hz, 1H). 13C
NMR (100 MHz, CDCl3): δ, 186.9, 153.0, 146.6, 146.3, 146.2, 130.1,
127.2, 117.7, 112.3, 108.7, 104.7, 100.8, 72.6, 63.0, 45.5, 28.8. HRMS
(ESI, m/z): calculated for C16H14NaO5 ([M + Na]+), 309.0733;
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325.1076; [α]D = +76.92 (c = 0.65, CHCl3, 99% ee). The
enantiomeric ratio was determined by HPLC analysis using a Daicel
Chiralpak IC-3 column (hexane/2-propanol = 40:60, flow rate 1.0
mL/min, λ = 254 nm), tR = 32.4 min (major), tR = 27.9 min (minor).
2-(8,9-Dihydro-6H-[1,3]dioxolo[4,5-f ]isochromen-6-yl)-1-(furan-
2-yl)ethanone (2o). 28 mg; 80% yield; Rf = 0.28 (20:80 = EtOAc/n-
hexane); colorless crystalline solid; mp. 138−140 °C. FT-IR (neat):
2921, 2853, 2320, 1667, 1568, 1467,1393, 1255, 1098, 1049, 919, 767
cm−1. 1H NMR (400 MHz, CDCl3): δ, 7.58 (d, J = 1.0 Hz, 1H), 7.22
(d, J = 3.4 Hz, 1H), 6.62 (dd, J = 37.6, 8.1 Hz, 2H), 6.53 (dd, J = 3.5,
1.7 Hz, 1H), 5.95 (s, 2H), 5.34 (dd, J = 9.1, 3.0 Hz, 1H), 4.10 (m,
1H), 3.74 (m, 1H), 3.39 (dd, J = 15.4, 9.1 Hz, 1H), 3.15 (dd, J = 15.4,
3.6 Hz, 1H), 2.82 (m, 1H), 2.64 (dt, J = 16.5, 3.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ, 186.9, 153.0, 146.6, 145.4, 144.9, 131.2, 117.7,
117.3, 116.3, 112.3, 106.4, 101.1, 72.7, 62.6, 45.4, 22.8. HRMS (ESI,
m/z): calculated for C16H14NaO5 ([M + Na]+), 309.0733; found,
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found, 309.0762; [α]D = +119.66 (c = 0.83, CHCl3, 93% ee). The
enantiomeric ratio was determined by HPLC analysis using a Daicel
Chiralpak IC-3 column (hexane/2-propanol = 70:30, flow rate 1.0
mL/min, λ = 254 nm), tR = 34.1 min (major), tR = 26.8 min (minor).
2-(8-Fluoroisochroman-1-yl)-1-(furan-2-yl)ethanone (2k). 21 mg;
81% yield; Rf = 0.22 (20:80 = EtOAc/n-hexane); colorless crystalline
solid; mp. 104−106 °C. FT-IR (neat): 2921, 2853, 2355, 2337, 1651,
1468, 1246, 1100, 1019, 763, 468 cm−1. 1H NMR (400 MHz, CDCl3):
δ, 7.58 (d, J = 0.9 Hz, 1H), 7.23 (d, J = 3.3 Hz, 1H), 7.14 (dd, J = 13.8,
7.9 Hz, 1H), 6.90 (t, J = 9.0 Hz, 2H), 6.53 (dd, J = 3.5, 1.7 Hz, 1H),
5.40 (dd, J = 9.0, 2.9 Hz, 1H), 4.11 (m, 1H), 3.75 (m, 1H), 3.43 (dd, J
= 15.5, 9.1 Hz, 1H), 3.17 (dd, J = 15.5, 3.6 Hz, 1H), 2.92 (m, 1H),
2.73 (dt, J = 16.8, 3.7 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ,
186.6, 160.4 (d, J = 245.0 Hz), 152.9, 146.6, 139.6 (d, J = 5.4 Hz),
127.0 (d, J = 8.5 Hz), 121.7 (d, J = 19.4 Hz), 120.0 (d, J = 3.3 Hz),
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309.0762; [α]D = +70.07 (c = 0.56, CHCl3, 88% ee). The
H
J. Org. Chem. XXXX, XXX, XXX−XXX